不同甲状腺形态的先天性甲状腺功能减退症患儿的遗传变异与临床特征:98例分析  

Genetic variation and clinical characteristics of children with congenital hypothyroidism with different thyroid morphology:an analysis of 98 cases

作　　者：张峰[1] 王瑛[2] 刘双[3] 王雷雷[3] 虞斌[1] 龙伟[4] Zhang Feng;Wang Ying;Liu Shuang;Wang Leilei;Yu Bin;Long Wei(Department of Medical Genetics,Changzhou Maternal and Child Health Care Hospital,Changzhou Medical Center Nanjing Medical University,Changzhou 213000,China;Department of Child Health,Changzhou Maternal and Child Health Care Hospital,Changzhou Medical Center,Nanjing Medical University,Changzhou 213000,China;Central Laboratory,Lianyungang Maternal and Child Health Care Hospital,Lianyungang 222000,China;Department of Medical Research Center,Changzhou Maternal and Child Health Care Hospital,Changzhou Medical Center,Nanjing Medical University,Changzhou 213000,China)

机构地区：[1]南京医科大学常州医学中心常州市妇幼保健院医学遗传科,常州213000 [2]南京医科大学常州医学中心常州市妇幼保健院儿童保健科,常州213000 [3]连云港市妇幼保健院中心实验室,连云港222000 [4]南京医科大学常州医学中心常州市妇幼保健院医学研究中心,常州1213000

出　　处：《中华围产医学杂志》2024年第8期649-655,共7页Chinese Journal of Perinatal Medicine

基　　金：常州市科技计划(CJ20220244);常州市卫健委资助项目(GN2023036)。

摘　　要：目的探讨不同甲状腺形态的先天性甲状腺功能减退症(congenital hypothyroidism,CH)患儿的遗传变异与临床特征差异。方法回顾性纳入2011年8月19日至2019年11月13日在南京医科大学常州医学中心常州市妇幼保健院及连云港市妇幼保健院确诊的CH患儿98例,按照甲状腺形态,将其分为甲状腺发育不全(thyroid dysplasia,TD)组(n=24)、原位甲状腺(gland-in-situ,GIS)组(n=67)和甲状腺肿大组(n=7)。采用全外显子组测序检测基因变异情况,将致病性、可能致病性及临床意义未明变异定义为潜在功能变异。比较3组CH患儿间的一般情况、基因变异及治疗情况。使用χ^(2)检验和Bonferroni校正、Kruskal-Wallis检验及Mann-Whitney U检验进行统计学分析。结果(1)TD组女婴比例高于GIS组和甲状腺肿大组[87.5%(21/24)与47.8%(32/67)和3/7,Bonferroni校正,P值均<0.017]。TD、GIS和甲状腺肿大组确诊CH时血清促甲状腺激素水平差异有统计学意义[128.00 mU/L(33.30~208.00 mU/L)、55.40 mU/L(17.73~116.00 mU/L)和32.00 mU/L(21.55~57.65 mU/L),H=7.02,P=0.030],但两两比较差异无统计学意义(P值均>0.017)。(2)基因潜在功能变异在TD、GIS、甲状腺肿大组中检出率分别为45.8%(11/24)、88.1%(59/67)和6/7,GIS组潜在功能变异检出率高于TD组(Bonferroni校正,P<0.001)。DUOX2基因潜在功能变异检出率最高[59.2%(58/98)],在TD、GIS及甲状腺肿大组中的检出率分别为20.8%(5/24)、73.1%(49/67)和4/7,组间差异有统计学意义(χ^(2)=20.02,P<0.001)。TD组中单等位基因变异更常见(7/11),而GIS组和甲状腺肿大组中双等位基因变异更常见,分别为71.2%(42/59)和4/6,此外在GIS患儿中还检出6例寡基因变异(10.2%,6/59)。(3)TD、GIS和甲状腺肿大组患儿左旋甲状腺素用药剂量(单位为μg/d)在2岁[37.50(25.00~45.00)、25.00(16.60~25.00)和25.00(16.50~40.00),H=16.53]及3岁[37.50(27.12~47.50)、20.00(6.25~29.25)和31.25(9.38~52.50),H=14.16]时差异均有统计学意义(P值均Objective To explore the differences in genetic variations and clinical features of children with congenital hypothyroidism(CH)with different thyroid morphologies.MethodsA retrospective study was conducted on 98 children with CH diagnosed at Changzhou Maternal and Child Health Care Hospital,Changzhou Medical Center,Nanjing Medical University,and Lianyungang Maternal and Child Health Care Hospital from August 19,2011,to November 13,2019.According to thyroid morphology,they were divided into the thyroid dysplasia(TD)group(n=24),the gland-in-situ(GIS)group(n=67),and the goiter group(n=7).Whole exome sequencing was used to detect genetic variants,and pathogenic,likely pathogenic variants,and variants of uncertain significance were defined as potential functional variants.General condition,genetic variants,and treatment were compared between the three groups.Statistical analysis was performed using Chi-square and Bonferroni correction tests,Kruskal-Wallis test,or Mann-Whitney U test.Results(1)The proportion of female infants in the TD group was higher than that in the GIS and goiter groups[87.5%(21/24)vs.47.8%(32/67)and 3/7,Bonferroni correction,respectively,both P<0.017].The difference in serum thyroid stimulating hormone levels when diagnosed with CH was statistically significant in the TD,GIS,and goiter groups[128.00 mU/L(33.30-208.00 mU/L),55.40 mU/L(17.73-116.00 mU/L),and 32.00 mU/L(21.55-57.65 mU/L),H=7.02,P=0.030],but was not statistically significant in pairwise comparisons(all P>0.017).(2)The detection rates of potential functional variants in the TD,GIS,and goiter groups were 45.8%(11/24),88.1%(59/67),and 6/7,respectively,and the detection rate in the GIS group was higher than that in the TD group(Bonferroni correction,P<0.001).The detection rate of potential functional variants in DUOX2 gene was the highest[59.2%(58/98)],which was 20.8%(5/24),73.1%(49/67),and 4/7 in the TD,GIS,and goiter groups,respectively,with statistically significant differences between groups(χ^(2)=20.02,P<0.001).Single allele variant

关 键 词：先天性甲状腺功能减退症 甲状腺发育不全 原位甲状腺 甲状腺肿 全外显子组测序 

分 类 号：R725.8[医药卫生—儿科]